Ok... looks like there is serious misunderstanding on this subject. Someone via email just said MAO-A is found in the Gut, you say its MAO-B. I'm going to continue quoting (I'm not making this up) a well known, well established book (A primer for Drug action)... here is another piece for you about MAOIs...
and on tryamine and MAO:
"Recently two subtypes of MAO have been identified. MAO-A is found in norepinephrine and serotonin nerve terminals in the brain (locus caeruleus), in human placenta, in intestine, and in peripheral norepinephrine-secreting nerve terminals. MAO-B is found in neurons (usually dopamine-secreting) in the brain (dorsal raphe nucleus) [so yes, MAO-B is in the brain too] and in blood platelets (a component of blood that is responsible for the initiation of clotting). The older, irreversible MAO inhibitors are nonselective and inhibit both forms of the enzyme; the inhibition of MAO-A is responsible for the antidepressant activity, and the inhibition of MAO-B is responsible for side-effects, including serious drug interactions that occur when the patient eats cheeses and other foods."
"MAO is not only responsible for regulation of intercellular levels of norepinephrine, serotonin [this explains why DMT and LSD is potentiated], and dopamine [this explains the amphetamines and cocaine], but also for hepatic (liver) metabolism of transmitter-like substances, such as tryamine (metabolized by MAO-B) [There you have it folks!]. Tyramine is a substance that is widely found in foods... [foods with tyramine in them]... The presence of tyramine in the body from such sources, which potentially can occur when MAO is inhibited, can precipitate a hypertensive crisis that is characterized by severe increases in blood pressure, intense headaches, increased heart rate, palpitations, and other effects that can be serious or fatal. Thus food limitations are required of patients who take NON-SPECIFIC MAO inhibitors."
Now I hope that will put a little more light on the issue. It makes a hell of a lot more sense than anything I've heard going around, and not only attributes the reason why irreversible MAOIs do damage, but also explains why specific MAO-A inhibitors don't!
I'm going to do self experiments with P. harmala and tyramine to prove it...
I'm becoming more and more interested in these medical selective reversible MAOIs.
Here is a quote from "A Primer of Drug Action (sixth edition):
"Several short-acting, selective, reversible MAO inhibitors are being investigated. The one that is currently of most interest is moclobemide [ed- it doesn't say why, anyone know why?]. All these drugs are highly selective in their ability to inhibit MAO-A, and are all reversible in action. Thus, they have a much improves safety profile. These drugs block MAO-A, which is responsible for their antidepressant effects, but do not block MAO-B, which leaves the tyramine metablosim unaffected (thus, the "cheese syndrome" is less of a concern). In addition, unlike the effects of the older compounds, REM sleep is relatively unaffected by these drugs."It seems from this that MAO-B is responsible for causing the "cheese syndrome" and not MAO-A, which is what we psychonauts like to potentiate things with.
In conclusion, I'm speculating (read as: SPECULATING), that since P. Harmala is an MAO-A specific MAOI it doesn't even affect tyramine metabolism, which explains why I'm still alive ;-) Mother Nature is truly amazing....
I'm going out on a limb and say Primer of Drug Action is wrong! Look at the following:
"Dopamine, tyramine, and tryptmine appear to be equally good substrates for both forms of the enzyme [MAO-A and MAO-B]"- p 246, Biochemical Basis of Neuropharmacology (6th edition), Cooper, Bloom, & Roth.
"The prefered substrate for MAO-A is serotonin, but it also deanimates noradrenaline and dopamine. The prefered substrate for MAO-B is benzylamine [?]. Tyramine and tryptamine are substrates for both types."- p 267, Brain Function and Psychotropic Drugs, Heather Ashton.
"The small-intestine and stomach contain MAO-A (Hasan, "The involvement of intestinal MAO in the transport and metabolism of tyramine", J Neural Transm 26 (suppl):1-9, 1988). MAOI's interfere with the catabolism of tyramine at these sites and allow the parenteral absorbtion of tryptamine entheogens...
Moclobemide...is considered relatively safe in the presence of dietary tyramine since it shows only a 4-5 fold increase in tyramine sensitivity leading to hypertension (30 mg or greater change in systolic BP). This corresponds to ingesting about 100 mg of oral tyramine since 400-500 mg of tyramine alone causes hyertension. Tranylcypromine (parnate) has a 50-fold increase in sensitivity (6 mg of tyramine is enough)...Such calculations, I believe, have not been done with the harmalas. However, harmaline has already been shown to be a stronger MAOI-A than moclobemide [Gerardy, below]..."- post from John Halpern, (email@example.com) who has also written warnings about the harmalas and diet in the MAPS newsletter (Autumn 1995, pp 58; should be at their Web site).
"Harmaline was more potent than moclobemide as an MAO-A inhibitor"
"...harmaline at a dose of 10 mg/kg had a similar potency to moclobemide at a dose of 50 mg/kg in inhibiting MAO-A"- Jean Gerardy, "Effect of moclobemide on rat brain MAO-A & B: comparison with harmaline and clorgyline", Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1994, Vol 18, pp 793-802.
[This was in rats. Normal human dose of harmaline for ayahuasca is 1.25 mg/kg (Ott), and for moclobemide about 4 mg/kg (from package insert); in this case the 8 times overdose of harmaline was the same as the 12 times overdose of moclobemide, making the harmaline look 1.5 times stronger. I'm sure there are many other variables, especially species and substrate used to measure activity in this case.]
"During studies conducted at the maximum recommended moclobimide dose of 600 mg/day, the mean dose of tyramine required to produce a 30 mm Hg increase in systolic blood pressure was 148 +/- 50 mg when moclobimide was administered immediately after tyramine. The threshold dose of tyramine was reduced to 84 +/- 23 mg when the seqence of administration was reversed so that moclobemide was administered one hour before tyramine. These findings indicate that the potentiation of tyramine may be minimized by administering moclobemide after, instead of prior to, a tyramine-enriched meal."- Manerix (moclobemide) package insert
"A few cheeses have high tyramine levels; NY State Cheddar has about 42 mg per 30 g serving, and Gruyere about 15 mg. But most cheeses and red wines are more like 5 mg per serving."- post from Nick Cozzi, prof of neurophysiolgy, University of Wisconsin. So eating a few ounces of the right cheese an hour after taking moclobemide or harmaline could lead to the 30 mm Hg increase in blood pressure (which is noticeable but not that much, I would guess).
Pure harmaline is a stronger MAO-A inhibitor than harmine. Syrian Rue has a a mix of both (about 50-50; varies somewhat by season of harvest, I've heard). This would make Rue roughly equivalent to moclobemide. (B. caapi has mostly harmine, about 158 mg per dose [Ott] and there's also tetra-hydro-harmine.)
I have a 2-inch file on this topic, but am still missing some key refs and much study. I have no particular conclusions, except that caution is advised for now.
Careful testing of blood pressure effects with, say, 3 g of Rue (or better, a pure 50/50 harmaline/harmine mix at 75 or 100 mg each) taken with small amounts of tyramine (say 10-20 mg at first; available at health food stores) taken concurrently would make sense, I think. Perhaps an experimental pharmacologist out there could suggest a simple protocol several of us could try at home.
Most will find this dull...you've been warned.
This is from Encyclopedia of Neuroscience Vol II 1987, p 676, Denis L. Murphy on MAOIs
clorgyline (an acetylenic MAOI) is a MOA-A inhibitor and effects deanimation of seratonin at concentrations 1000x lower than it needs to effect deanimation of phenylethylamine and other subtrates of MOA-B. deprenyl (an acetylenic MAO-B inhibitor) is just the opposite. Dopamine is a MOA-B subtrate. noradrenline is an MAO-A subtrate. In high MAOI doses the brain becomes flooded with monoamines. [my note - this may account for the diferences in how a trip develops with the rooster booster.] MAO-A inhibition surpresses REM. The BP swings a blamed on norepinephrine. Large scale studies indicate such bp swings are rare.
Hope this was useful.
Okay, I just thought that I would add some more thoughts to clarify/confuse this issue.
In a discussion of Deprenyl in the book Smart Drugs II: The Next Generation Dean, Morgenthaler & Fowkes state:
Okay, the above "simple" explaination was provided to clarify some ideas about MAO-A and MAO-B. The information below, from a recent letter to me from Jonathan Ott, is the confusing bit:
"MAO enzymes are found throughout the body and come in two known types: type A (found in most body tissues), and type B (found predominatly in brain glial cells). Glial cells are small brain cells which surround and metabolically support the neurons which conduct the electrical signals throughout the brain.
"Most MAO inhibitors are unselective, inhibiting both MAO-A and MAO-B to a similar degree. When MAO-A is inhibited (as with amphetamines, for example), a dangerous high-blood-pressure reaction can occur in patients who eat certain foods like aged cheeses, chianti wines, and chicken liver pate, which contain a chemical called tyramine. Tyramine is usually metabolized by MAO, and the inhibition of MAO causes tyramine to dangerously accumulate. This same high-blood-pressure reaction can occur in patients taking L-dopa for Parkinson's disease. Unlike other MAO inhibitors, however, deprenyl inhibits only MAO-B. It does not cause the 'Cheese reaction' and it can be safely administered with L-dopa.
"Deprenyl was the first selective MAO-B inhibitor to be described in the scientific literature. Over the last 30 years, it has become the reference standard for MAO-B inhibition. It is still the only one in widespread clinical use today."
"For the record, seeds of P. harmala and the B-carboline alkaloids in particular do not potentiate tryptamines in ayahuasca. Potentiate, in pharmacology, is a nonce-word meaning 'to make more potent' and, while the B-carbolines do render DMT and other tryptamines orally-active, as such they are decidedly less potent than they are when smoked or injected. In no way, then, do B-carbolines potentiate these tryptamines. Some experts on this subject, who should know better, have carelessly misused the term potentiate in this context. Nor does it follow that the B-carbolines or harmel seeds potentiate any other entheogens with effects analogous to the tryptamines. There is experimental and anecdotal evidence in human subjects, that MAO inhibitors, far from potentiating the effects of LSD, antagonize these and may even block them fully or partially [the MAOI Marplan clearly blocked the effects of LSD in human subjects: Resnick, O. et. al. 1964. Life Sciences 11(3): 1207-1214; and a survey by NIMH researchers found that MAOI use caused "a decrease in response to LSD" Bonson, K. MAPS 5 (1): 9, 1994]. It was shown experimentally that the MAOI iproniazid or Marsiliod caused "less pronounced" sensitivity of human subjects to injected DMT [Sai-Halasz, A. Psychopharmacologica 4: 385-388, 1963] which is consistent with my psychonautic bioassay data reported in Ayahuasca Analouges - oral activity but diminished potency of DMT in ayahuasca as opposed to by other routes. I presented very limited data suggesting a possible potentiation of mescaline by B-carbolines [based on only two psychonautic bioassays by one volunteer], and I have heard considerable noise to the effect that harmel seeds can potentiate the effects of psilocybian mushrooms, but not one single solid data point demonstrating this exists to my knowledge. Given the experimental evidence that different MAOI antagonize the effects of DMT and LSD, any potentiation of psilocybine by MAOI would be surpising."
(My hands are tired now from typing - I assure you that any typos in the above quote are probably mine, not Ott's!).
I think that Ott is wrong, relying too much on "studies" and not at all on personal experience. My own experience, the experience of others on this list, and the experience of numerous people I have spoken with, shows that harmel seeds do potentiate LSD, DMT, mescaline, and psilocybian mushrooms. Perhaps this varitey of different people who have reported "potentiation" on trips with psilocybian mushrooms is the "noise" which Ott refers to. When I wrote him back, I gave numerous examples (including one from this list - sorry, I don't remember who sent it to me - about a smoked DMT trip potentiated by deprenyl). My last paragraph to Ott regarding this subject stated:
"I can only see one way to resolve this issue in your mind, aside from studies and chemical testing. That would be for you to take Psilocybe mushrooms with Peganum harmala and see how it effects you. Perhaps you have already done this, and experienced no potentiation (which would make your opinion understandable to me). However, if you haven't tried this, I think that your opinion would fall under Wasson's comments about Psilocybe mushrooms: "those who have taken the mushrooms (with P. harmala) and are disqualified by our subjective experience, and those who have not taken the mushrooms (with P. harmala) and are disqualified by their total ignorance of the subject!"I'm looking forward to his response.
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